The purification from adult and neonatal rat livers of glucocorticoid-receptor complex to near homogeneity will be attempted using procedures that already have proved successful. These procedures include precipitation with MnCl2 of the cytosol preparation and affinity chromatography using heparin-coupled agarose. In addtion, gel filtraion and DNA and DEAE cellulose chromatographic techniques will be employed. Detailed physico-chemical studies will be made of the properties of the purified hepatic glucocorticoid-receptor complex from neonatal and adult rat livers in order to establish similarities and differences in adult and neonatal receptor proteins. By judicious use of techniques and approches previously developed and used by us, I shall examine the developmentally related changes in (a) the nature of hepatic glucocorticoid receptor, (b) the rate and nature of hepatic glucocorticoid activation, and (c) the glucocorticoid-induced increase in RNA synthesis on chromatin template. New methods and approaches will be developed as necessary including a hepatic cytosol glucocorticoid-exchange assay. Such an assay may allow estimation of the total bound and unbound cytoplasmic glucocorticoid receptor concentrations. The study of mechanism by which glucocorticoids control a differential gene expression in rat liver will promote an understanding on the steroid hormone induced cell development and differentiation. Significance of this problem obviously extends beyond this particular system.